Dopaminergic neurotransmission plays a crucial role in the genesis and maintenance of alcohol dependence. Epigenetic regulation via promoter specific DNA methylation of the dopamine transporter gene (DAT) may influence altered dopaminergic neurotransmission in alcoholism. Aim of the present study was to investigate DNA promoter methylation of DAT in early alcohol withdrawal and in relation to alcohol craving. We analyzed blood samples of 76 patients admitted for detoxification treatment and compared them to 35 healthy controls. Methylation specific quantitative real-time PCR was used to measure the promoter specific DNA methylation of the dopamine transporter. We assessed the extent of alcohol craving using the obsessive compulsive drinking scale (OCDS). Compared to healthy controls we found a significant hypermethylation of the DAT-promoter (Mann-Whitney U-test: p = 0.001). Ln-transformed methylation of the DAT-promoter was negatively associated with the OCDS (linear regression: Beta = -0.275, p = 0.016), particularly with the obsessive subscale (Beta = -0.300, p = 0.008). Findings of the present study show that the epigenetic regulation of the DAT-promoter is altered in patients undergoing alcohol withdrawal. Furthermore, hypermethylation of the DAT-promoter may play all important role in dopaminergic neurotransmission and is associated with decreased alcohol craving. (C) 2008 Elsevier Ltd. All rights reserved.
机构:
Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USAEmory Univ, Dept Epidemiol, Atlanta, GA 30322 USA
McCullough, Lauren E.
Collin, Lindsay J.
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Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USAEmory Univ, Dept Epidemiol, Atlanta, GA 30322 USA
Collin, Lindsay J.
Conway, Kathleen
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Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USAEmory Univ, Dept Epidemiol, Atlanta, GA 30322 USA
Conway, Kathleen
White, Alexandra J.
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机构:
NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USAEmory Univ, Dept Epidemiol, Atlanta, GA 30322 USA
White, Alexandra J.
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机构:
Cho, Yoon Hee
Shantakumar, Sumitra
论文数: 0引用数: 0
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机构:
GlaxoSmithKline, Epidemiol Real World Evidence & Digital Platforms, Singapore, SingaporeEmory Univ, Dept Epidemiol, Atlanta, GA 30322 USA
Shantakumar, Sumitra
Terry, Mary Beth
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机构:
Columbia Univ, Dept Epidemiol, New York, NY 10032 USAEmory Univ, Dept Epidemiol, Atlanta, GA 30322 USA
Terry, Mary Beth
Teitelbaum, Susan L.
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机构:
Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY 10029 USAEmory Univ, Dept Epidemiol, Atlanta, GA 30322 USA
Teitelbaum, Susan L.
Neugut, Alfred, I
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机构:
Columbia Univ, Dept Epidemiol, New York, NY 10032 USA
Columbia Univ, Dept Med, New York, NY 10032 USAEmory Univ, Dept Epidemiol, Atlanta, GA 30322 USA
Neugut, Alfred, I
Santella, Regina M.
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Columbia Univ, Dept Environm Hlth Sci, New York, NY 10032 USAEmory Univ, Dept Epidemiol, Atlanta, GA 30322 USA
Santella, Regina M.
Chen, Jia
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机构:
Columbia Univ, Dept Epidemiol, New York, NY 10032 USA
Icahn Sch Med Mt Sinai, Dept Pediat, New York, NY 10029 USA
Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 USAEmory Univ, Dept Epidemiol, Atlanta, GA 30322 USA
Chen, Jia
Gammon, Marilie D.
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机构:
Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USAEmory Univ, Dept Epidemiol, Atlanta, GA 30322 USA
机构:
Natl Def Med Ctr, Grad Inst Med Sci, Taipei, Taiwan
Triserv Gen Hosp, Natl Def Med Ctr, Dept Neurol, Taipei, TaiwanNatl Def Med Ctr, Grad Inst Med Sci, Taipei, Taiwan
Yen, Che-Hung
Shih, Mei-Chen
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Triserv Gen Hosp, Natl Def Med Ctr, Dept Psychiat, 325 Cheng Kung Rd,Sec 2, Taipei 11490, TaiwanNatl Def Med Ctr, Grad Inst Med Sci, Taipei, Taiwan
Shih, Mei-Chen
Cheng, Cheng-Yi
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Triserv Gen Hosp, Natl Def Med Ctr, Dept Nucl Med, Taipei, TaiwanNatl Def Med Ctr, Grad Inst Med Sci, Taipei, Taiwan
Cheng, Cheng-Yi
Ma, Kuo-Hsing
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机构:
Natl Def Med Ctr, Dept Anat & Biol, Taipei, TaiwanNatl Def Med Ctr, Grad Inst Med Sci, Taipei, Taiwan
Ma, Kuo-Hsing
Lu, Ru-Band
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机构:
Natl Cheng Kung Univ, Coll Med, Inst Behav Med, Tainan, TaiwanNatl Def Med Ctr, Grad Inst Med Sci, Taipei, Taiwan
Lu, Ru-Band
Huang, San-Yuan
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Natl Def Med Ctr, Grad Inst Med Sci, Taipei, Taiwan
Triserv Gen Hosp, Natl Def Med Ctr, Dept Psychiat, 325 Cheng Kung Rd,Sec 2, Taipei 11490, TaiwanNatl Def Med Ctr, Grad Inst Med Sci, Taipei, Taiwan
机构:
Xavier Bichat Univ, U675, Fac Bichat,IFR02, INSERM, F-75018 Paris, France
Hop Louis Mourier, Psychiat Serv, AP HP, F-92701 Colombes, FranceXavier Bichat Univ, U675, Fac Bichat,IFR02, INSERM, F-75018 Paris, France
Le Strat, Yann
Ramoz, Nicolas
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机构:Xavier Bichat Univ, U675, Fac Bichat,IFR02, INSERM, F-75018 Paris, France
Ramoz, Nicolas
Pickering, Paul
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h-index: 0
机构:
Xavier Bichat Univ, U675, Fac Bichat,IFR02, INSERM, F-75018 Paris, France
Hop Louis Mourier, Psychiat Serv, AP HP, F-92701 Colombes, FranceXavier Bichat Univ, U675, Fac Bichat,IFR02, INSERM, F-75018 Paris, France
Pickering, Paul
Burger, Virginie
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h-index: 0
机构:Xavier Bichat Univ, U675, Fac Bichat,IFR02, INSERM, F-75018 Paris, France
Burger, Virginie
Boni, Claudette
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h-index: 0
机构:Xavier Bichat Univ, U675, Fac Bichat,IFR02, INSERM, F-75018 Paris, France
Boni, Claudette
Aubin, Henri-Jean
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h-index: 0
机构:
AP HP, Serv Med Interne Alcool, Limeil Brevannes, FranceXavier Bichat Univ, U675, Fac Bichat,IFR02, INSERM, F-75018 Paris, France
Aubin, Henri-Jean
Ades, Jean
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h-index: 0
机构:
Xavier Bichat Univ, U675, Fac Bichat,IFR02, INSERM, F-75018 Paris, France
Hop Louis Mourier, Psychiat Serv, AP HP, F-92701 Colombes, FranceXavier Bichat Univ, U675, Fac Bichat,IFR02, INSERM, F-75018 Paris, France
Ades, Jean
Batel, Philippe
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机构:
UTAMA, AP HP, Clichy, FranceXavier Bichat Univ, U675, Fac Bichat,IFR02, INSERM, F-75018 Paris, France
Batel, Philippe
Gorwood, Philip
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机构:Xavier Bichat Univ, U675, Fac Bichat,IFR02, INSERM, F-75018 Paris, France
机构:
Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA
Univ Iowa, Neurosci & Genet Programs, Iowa City, IA 52242 USAUniv Iowa, Dept Psychiat, Iowa City, IA 52242 USA
Philibert, Robert A.
Gunter, Tracy D.
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机构:
Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USAUniv Iowa, Dept Psychiat, Iowa City, IA 52242 USA
Gunter, Tracy D.
Beach, Steven R. H.
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机构:
Univ Georgia, Athens, GA 30602 USAUniv Iowa, Dept Psychiat, Iowa City, IA 52242 USA
Beach, Steven R. H.
Brody, Gene H.
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机构:
Univ Georgia, Athens, GA 30602 USAUniv Iowa, Dept Psychiat, Iowa City, IA 52242 USA
Brody, Gene H.
Madan, Anup
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机构:
Inst Syst Biol, Seattle, WA USAUniv Iowa, Dept Psychiat, Iowa City, IA 52242 USA